Coincident with an increase in human life-span is the recent increase in the incidence of metabolic bone diseases, such as osteoporosis, bone fracture, and bone pain etc. In bone tissue, bone formation and bone resorption are always taking place. While the balance of bone formation and bone resorption takes place in one's youth, bone resorption exceeds bone formation due to various causes as one ages, ("uncoupling"). Prolonged bone resorption causes bone tissue to become fragile, resulting in metabolic bone diseases, such as osteoporosis, bone fracture, bone pain, etc. Accordingly, if uncoupling could be inhibited, metabolic bone diseases such as osteoporosis, bone fracture, bone pain, etc. may be prevented.
Conventional methods of preventing or treating metabolic bone diseases by inhibiting uncoupling include, but are not limited to, (1) dietary calcium supplementation, (2) light exercise, (3) sunbathing and (4) medicinal therapy, etc. are exemplified. Calcium supplements include calcium salts, such as calcium carbonate, calcium phosphate, etc., and naturally occurring calcium-containing preparations, such as bovine bone powder, egg shell, fish bone powder, etc. They are, however, not necessarily suitable for oral administration. Light exercise, jogging or walking are also recommended. However, these activities are troublesome to a person who has become weak or is an immobilized elderly person. Sunbathing is believed to be beneficial for supplementing the active form of vitamin D.sub.3 but is not sufficient as therapy. A medicinal therapy, such as 1.alpha.-hydroxyvitamin D.sub.3 and/or calcitonin, may be used as an effective treatment for osteoporosis. However, these compounds are medicines and can not be used as food supplements.
The present inventors have discovered that a fraction obtained from whey protein was effective for strengthening bone (Japanese published unexamined patent application No. 183371 (1992)). Further, the present inventors found that a subfraction obtained from the above bone strengthening fraction by treating with ethanol, heating, treating with salts or treating with ultrafiltration membrane was effective for stimulating proliferation of osteoblasts and for strengthening bone (Japanese published unexamined patent application No. 176715 (1993), Japanese published unexamined patent application No. 320066 (1993)). In addition, the present inventors found that the basic protein fraction present at very low levels in milk was able to stimulate proliferation of osteoblasts, strengthen bone and prohibit bone resorption (Japanese patent application No. 207509(1995)).
The present inventors found that a basic protein composition obtained from milk-derived basic protein fractions by various kinds of treatment thereof had the activity of stimulating osteoblast proliferation, strengthening bone and inhibiting bone resorption. Further, the inventors found that a basic peptide composition obtained from the above basic protein composition by protease degradation also had the activity of stimulating osteoblast proliferation, strengthening bone and inhibiting bone resorption.